Topical film-forming compositions are commonly used in the treatment of various tissues aliments including cold sores, canker sores, chapped lips, bums, cuts, abrasions, etc. Such compositions are designed to form a protective film over the tissue area of application. Furthermore, these compositions may serve as carriers for various medicinal, antibiotic, antifungal, anesthetic, analgesic and virucidal agents as well as related components such as penetration enhancers (e.g. AZONE). Examples of such film-forming compositions include those disclosed in U.S. Pat. Nos. 4,381,296 and 4,285,934 both to Tinnell, Re. 33,093 to Schiraldi et al., and 5,081,157 to Pomerantz.
The effectiveness of topical film-forming compositions is highly dependent upon the mechanical properties of the film ultimately formed upon the tissue site. That is, to be effective, film-forming compositions must be capable of adhering to tissues, including moist mucosal tissue, e.g. as in oral applications. Furthermore, the resultant film must resist abrasion and irrigation by body fluids. Perhaps most importantly, such films must be flexible, as the tissues to which they are adhered to, stretch and flex.
One class of known film-forming compositions use ethyl cellulose film-formers with esterification agents. These compositions tend to produce brittle films which are likely to separate from their sites of application. While not wishing to be bound by theory, it is believed that the brittle nature of these films is a result of the use of ethyl cellulose, which only undergoes esterification at sites on the cellulose backbone.
Another class of known film-forming compositions utilize hydroxypropyl cellulose with esterifications agents. These compositions do not exhibit the same degree of brittleness, as with ethyl cellulose. This is believed to be due to the presence of hydroxyl groups on side chains from the cellulose backbone, which are capable of esterification. One drawback to these compositions, however, is that they tend to be relatively weak and often do not maintain their integrity. As such, films formed from such compositions are commonly displaced shortly after their application. The addition of crosslinking agents to these compositions can increase the strength of films formed thereby, but such crosslinking can render the film quite brittle.
For example, U.S. Pat. No. 5,081,157 to Pomerantz discloses a topical film-forming composition which includes: 1) hydroxypropyl cellulose, 2) a non-toxic volatile solvent, e.g. an alcohol, 3) an esterification agent, e.g. a carboxylic acid, 4) a boric acid crosslinking agent, and 5) medicinal compounds, e.g. hydrocortisone, lidocaine hydroclholoride, benzocaine, etc. As described in the reference, the carboxyl groups of the esterification agent (e.g. tannic acid and salicyclic acid) undergo esterification with the hydroxypropyl cellulose. Following and/or during esterification, boric acid crosslinks parts of the ester. This crosslinking adds strength to the resulting film; however, since boric acid has three hydroxyl groups, it is capable of crosslinking the ester at three locations. These three locations are only separated by an interstitial boron atom. Although not wishing to be bound by theory, it is believed that the crosslinked portions of the ester(s) are drawn too close together due to the close proximity of the three hydroxyl groups of boric acid, thus forming a rigid opaque film. As a result, the film formed tends to be thick and brittle, causing it to frequently crack and dislodge from its point of application. Furthermore, compositions including boric acid are known to cause skin irritation for many individuals.
Thus, strong, yet flexible, non-irritating film-forming compositions are sought which readily adhere to moist tissues.